Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Mar 22, 2016; 6(1): 43-53
Published online Mar 22, 2016. doi: 10.5498/wjp.v6.i1.43
Cortical and subcortical gamma amino acid butyric acid deficits in anxiety and stress disorders: Clinical implications
Andrew W Goddard
Andrew W Goddard, Department of Psychiatry, UCSF Fresno Medical Education and Research Program, Fresno, CA 93701, United States
Author contributions: Dr. Goddard AW reviewed the literature and wrote the manuscript.
Conflict-of-interest statement: Royalties for manuscript production for UpToDate. No financial support for the current review paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Andrew W Goddard, MD, Professor of Psychiatry, Department of Psychiatry, UCSF Fresno Medical Education Program, 155 N. Fresno Street, Fresno, CA 93701, United States. agoddard@fresno.ucsf.edu
Telephone: +1-559-4996580 Fax: +1-559-4996581
Received: October 27, 2015
Peer-review started: November 3, 2015
First decision: December 4, 2015
Revised: December 18, 2015
Accepted: January 27, 2016
Article in press: January 29, 2016
Published online: March 22, 2016
Processing time: 141 Days and 9.2 Hours
Abstract

Anxiety and stress disorders are a major public health issue. However, their pathophysiology is still unclear. The gamma amino acid butyric acid (GABA) neurochemical system has been strongly implicated in their pathogenesis and treatment by numerous preclinical and clinical studies, the most recent of which have been highlighted and critical review in this paper. Changes in cortical GABA appear related to normal personality styles and responses to stress. While there is accumulating animal and human neuroimaging evidence of cortical and subcortical GABA deficits across a number of anxiety conditions, a clear pattern of findings in specific brain regions for a given disorder is yet to emerge. Neuropsychiatric conditions with anxiety as a clinical feature may have GABA deficits as an underlying feature. Different classes of anxiolytic therapies support GABA function, and this may be an area in which newer GABA neuroimaging techniques could soon offer more personalized therapy. Novel GABAergic pharmacotherapies in development offer potential improvements over current therapies in reducing sedative and physiologic dependency effects, while offering rapid anxiolysis.

Keywords: Brain imaging; Anxiogenesis; Gamma amino acid butyric acid; Anxiety disorders; Anxiolysis

Core tip: Preclinical and clinical studies strongly support the notion that impairments in gamma amino acid butyric acid (GABA) neurotransmission underpin human stress and anxiety disorders. Measurement of in-vivo brain GABA function with modern neuroimaging tools, such as proton magnetic resonance spectroscopy, in healthy and disease populations, has contributed greatly to this literature, and also offers the possibility of monitoring GABAergic anxiolytic therapy.